The maintenance of the characteristic shape of the human erythrocyte as well as the deformability of its cell membrane is a function central to the normal rheologic properties of these cells. These functions are impaired in a variety of hemolytic states. A body of indirect evidence suggests that an actomyosin-like protein complex call Spectrin, disposed on the inner surface of the erythrocyte membrane, is involved in the maintenance of these functions. We have observed as have others, that isolated erythrocyte membranes catalyze the phosphorylation of endogenous peptides, among which is a peptide of molecular weight 200,000 which is a component of the Spectrin complex. This observation suggests to us a means by which the intracellular metabolic state of the erythrocyte may regulate the structure and function of its plasma membrane. Consequently, we are attempting to characterize the protein kinase and phosphatase systems that mediate Spectrin phosphorylation, and relate these changes in Spectrin phosphorylation to the structural and functional state of the erythrocyte membrane. Initial studies have delineated two membrane bound protein kinases, one independent of cyclic AMP and highly specific for Spectrin, and a second, stimulated by cyclic AMP, specific for certain minor membrane peptides. We have identified a phosphoprotein phosphatase as well. Our studies in intact erythrocytes indicate that Spectrin is the major naturally occurring membrane phosphopeptide. The regulation of these reactions and their relation to the control of membrane structure are currently under study.